ps-341 in treating patients with metastatic neuroendocrine tumors

Conditions: Gastrointestinal Carcinoid Tumor; Islet Cell Tumor

Summary: rationale: drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. purpose: phase ii trial to study the effectiveness of ps-341 in treating patients who have metastatic neuroendocrine tumors.

objectives: * determine the objective response rate of patients with metastatic neuroendocrine tumors treated with bortezomib. * determine the toxicity of this drug in this patient population. * determine the pharmacodynamics to correlate proteasome inhibition and efficacy of this drug in this patient population. outline: this is a multicenter study. patients receive bortezomib iv over 3-5 seconds on days 1, 4, 8, and 11. treatment repeats every 21 days for at least 8 courses in the absence of disease progression or unacceptable toxicity. patients achieving complete response (cr) receive 2 additional courses beyond cr. projected accrual: a total of 16-25 patients will be accrued for this study within 6 months.

Eligibility criteria:
disease characteristics: * histologically confirmed metastatic carcinoid tumor or islet cell tumor * well-differentiated neuroendocrine tumor or * well-differentiated neuroendocrine carcinoma * measurable disease in at least 1 dimension * at least 20 mm by conventional techniques or at least 10 mm by spiral ct scan * the following are considered nonmeasurable: * lesions in a previously irradiated area * bone lesions * leptomeningeal disease * ascites * pleural/pericardial effusion * lymphangitis cutis/pulmonis * abdominal masses that are not confirmed and followed * cystic lesions patient characteristics: age: * 18 and over performance status: * ecog 0-2 life expectancy: * at least 6 months hematopoietic: * leukocyte count at least 3,000/mm\^3 * absolute neutrophil count at least 1,500/mm\^3 * platelet count at least 100,000/mm\^3 hepatic: * bilirubin no greater than 1.5 mg/dl * ast/alt no greater than 2.5 times upper limit of normal renal: * creatinine no greater than 1.5 mg/dl cardiovascular: * no symptomatic congestive heart failure * no unstable angina pectoris * no cardiac arrhythmia other: * no other uncontrolled illness * no ongoing active infection * no psychiatric illness or social situation that would preclude study * no history of allergic reaction to compounds of similar chemical or biologic composition to bortezomib * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception prior concurrent therapy: biologic therapy: * at least 4 weeks since prior immunotherapy (interferon alfa) chemotherapy: * no more than 1 prior systemic chemotherapy regimen (except hepatic artery chemoembolization) * at least 4 weeks since prior systemic chemotherapy (6 weeks for nitrosoureas) * at least 12 weeks since prior hepatic artery chemoembolization (unless liver lesions are not indicator lesions) * stable dose long-acting octreotide therapy (sandostatin lar) within the past 3 months allowed * concurrent subcutaneous octreotide for breakthrough symptomatic relief allowed endocrine therapy: * not specified radiotherapy: * see disease characteristics * at least 4 weeks since prior radiotherapy surgery: * not specified other: * no other concurrent investigational agents, commercial agents, or therapies * no concurrent combination antiretroviral therapy for hiv-positive patients

Keywords: metastatic gastrointestinal carcinoid tumor gastrinoma insulinoma somatostatinoma glucagonoma